The present invention relates to membranes. In particular, the present invention relates to membranes including, but not limited to, thin membranes and to methods of making such membranes.
Generally membranes can be defined as selective barriers between two phases. Separation is achieved when some species are transported to a greater extent from one phase to the other. The driving force for the movement of molecules includes concentration differences, electric potential differences (charge) and pressure differences. The rate of transport of molecules through membranes is governed by several factors including pore size, thickness of membrane, membrane fouling rates, etc.
A wide variety of different materials have been utilized for producing membranes. Generally microporous membranes can be divided into two main groups: those formed physically and those formed chemically. Membranes can also be controllable formed by careful manipulation of the solubility of polymers in solution. These physically formed membranes can be produced by either diffusion induced phase separation techniques (DIPS) or temperature induced phase separation (TIPS).
Physically formed membranes are useful for many applications including water purification, dialysis and protein separation. However, the techniques for reliably producing membranes of controlled pore size are often complicated, expensive and not easily reproduced in the laboratory.
Chemically produced membranes are made via a series of chemical reactions to form three-dimensional polymer networks. Thin polymer networks are not generally mechanically strong and are often supported in order to make useful products. The support or substrate is generally made from a material that is relatively inert, has good wet strength and not likely to readily bind proteins. Examples of substrates that have been used previously include fiberglass, polyethyleneterapthalate (PET) and woven nylon.
Recently, a need has arisen for membranes having the following characteristics:
controlled pore size
provide rapid separation
good mechanical strength
be free of soluble impurities
defect free
water resistant
Current methods for producing suitable membranes produce relatively thick membranes with a tendency for large numbers of defects. Whilst they tend to have good mechanical strength, their thickness results in some disadvantages. First, they have slower separation times compared to thin membranes. Second, they require more processing (eg more washes) to remove soluble entities from the membrane. In the case of the aqueous system, water soluble entities are removed. It is highly desirable to remove such water soluble entities, for example residual monomer, as they may react with the species being separated, resulting in an impure product and possibly toxic in nature. In the case of the organic systems, organic soluble entities are removed.
Supported membranes have conventionally been formed on a substrate by casting a membrane-forming polymer between two glass plates. A characteristic of membranes formed by this process is that they have a glossy/shiny appearance. This glossy appearance is the result of the membrane having a continuous polymeric layer over the substrate (see FIG. 1(a)). That is, the resultant membrane is thicker than the substrate.
To produce a thinner membrane according to such conventional methods, a thinner substrate is used. In the case of non-woven substrates, as the substrate becomes thinner, the distance between the fibrils in the substrate increases. At a certain distance, the polymeric layer is no longer able to completely fill in the interstitial spaces between the fibrils of the substrate. This results in the formation of holes in the continuous polymeric layer, producing a defect and a non-functional membrane. In the case of woven substrates, as the substrate becomes thinner, the fibre diameter of the substrate decreases, and with it, a reduction in gel holding ability.
We have discovered that, surprisingly, a functional membrane can be achieved by filling the interstitial gaps or spaces in a substrate with a polymer, preferably crosslinked (see FIG. 1(b)), without forming a continuous constant thickness polymeric layer over the substrate as in the case of conventional membranes. Such membranes, because of their unique structure, have a matt or non-glossy appearance on at least one side, in contrast to the glossy appearance of membranes produced by the conventional methodology described above.
In a first aspect, the present invention provides a polymeric membrane system comprising a substrate and a polymeric membrane, wherein the substrate comprises a plurality of interstitial gaps therein and wherein the polymeric membrane comprises polymeric membrane components spanning the interstitial gaps of the support, the polymeric membrane components being thinner than the substrate.
Preferably the polymeric membrane system of the invention has no detectable soluble entities. In the case of aqueous systems, water soluble entities are not detectable. In the case of organic systems, organic soluble entities are not detectable. Most preferably, the system has no detectable residual monomer(s).
An advantage of forming the membrane in the interstitial gaps of the substrate is that the thickness of the support is not governed by the thickness of the membrane. Therefore, the thickness of each membrane component spanning the interstitial gaps can be decreased so that they are effectively below the surface of the substrate. Thus, the design of the membrane is such that a thin membrane can be achieved while using a substrate that is of sufficient thickness to provide the required mechanical strength for the particular application. An advantage of a thinner membrane is that more rapid separation times can be achieved. Moreover, a thinner membrane, requires less processing to remove soluble entities from the membrane.
The polymeric membrane of the first aspect of the invention may be a crosslinked or non-crosslinked polymeric membrane. Preferably, the polymeric membrane is a crosslinked polymer membrane.
Preferably, the thickness of the membrane components making up the membrane is in a range of about 0.01 mm to 0.5 mm.
The polymeric membrane system of the first aspect of the invention has particular (but not exclusive) application to thin membranes. Preferably, in this case, the thickness of the membrane components making up the membrane is in a range of about 0.01 to 0.1 mm, more preferably about 0.03 to 0.09 mm.
In a second aspect, the present invention provides polymeric system according to the first aspect wherein the polymeric membrane is an ultra-thin membrane.
The polymeric membrane of the polymeric membrane system of the present invention may be formed from any crosslinked or non-crosslinked polymer conventionally used to prepare membranes. Preferably, the membrane is a hydrophilic membrane.
The membrane may be any gel-forming polymer. The membrane may be an electrophoretic gel. Examples of suitable polymers include, but are not limited to polyacrylamide gels and poly HEMA with EGDMA.
The substrate is preferably formed from a material that is relatively inert, has good wet strength and does not bind to the substance undergoing separation (eg proteins). The substrate has a plurality of interstitial gaps therein. Preferably the size of the interstitial gaps is no greater than the thickness of the substrate. The substrate may be woven or non-woven. The substrate may be a woven or non-woven material or a textile. The substrate is in the form of a sheet, web, or any other appropriate form.
The substrate may be formed from any material that is conventionally used as a membrane support. Non-limiting examples of suitable materials for use as substrates include, but are not limited to polyvinyl alcohol, polyethyleneteraphthalate (PET), nylon and fiberglass, cellulose, cellulose derivatives, or any other suitable substrates. Preferably the substrate is hydrophilic nature in the case of aqueous solvent systems. In the case of an organic solvent system, the substrate is preferably possesses a similar hydrophilicity to the solvent used.
An example of a hydrophilic substrate material is polyvinyl alcohol. Polyvinyl alcohol paper has been found to be a suitable substrate. It is available in several different weights and thicknesses and may be used as the substrate without pre-treatment.
An example of a suitable substrate is Papylon, the trade name for the PVA1 paper (Sansho Corporation, The 2nd Kitahama Building 1-29, Kitaham-Higashi, Chuoh-Ku, Osaka, Japan, Ph: 06 6941 7895). Papylon has both excellent wet and dry strengths and has a very regular flat structure. We found that the two best performing were BFN No 2, which has a weight of 24.5 g/m2 and a thickness of 0.092 mm and BFN No. 3, which has a weight of 36.3 g/m2 and a thickness of 0.130 mm. The BFN No. 2 performed quite adequately and we used it to perform most of the tests described below.
A further example of a suitable substrate is heat bonded polyethyleneterephthalate. Because of its hydrophobic nature, PET requires some pre-treatment to enable better wetting of the surface by the aqueous monomer solution. The surface may be pretreated with a non-ionic surfactant, which renders the PET more hydrophilic while not introducing any charged groups into the system.
It is, however, preferable that no pre-treatment of the substrate is necessary.
In a third aspect, the present invention provides a method for the production of a polymeric membrane system of the first aspect, wherein a substrate having a plurality of interstitial gaps is contacted with at least one membrane-forming monomer and at least one crosslinker and subjecting the at least one monomer to polymerization.
Preferably, the method of the third aspect of the invention includes a treatment step to remove any soluble entities, for example, residual monomer, in the formed polymer to a point where the soluble entity (entities) are undetectable. In the case of aqueous system, water-soluble entities are not detectable. In the case of organic systems, organic soluble entities are not detectable. Most preferably, the system has no detectable residual soluble monomer(s), oligomers, initiator, etc.
The treatment may be one or more washing steps. As already mentioned above, the polymeric membrane system of the present invention is such that very thin membranes may be achieved. In the case where a very thin membrane is formed (eg an ultrathin membrane) as little as one wash may be required to render residual soluble entities to undetectable levels. Preferably the washing process is automated and the washing continued until there is no detectable soluble entities. This can optionally be computer controlled, driven by a feedback loop via an on-line detection system.
Residual entities, including monomer(s) can be measured by any of the appropriate well-established methods (see Reviews in Environmental Health, 9(4), 1991, 215-228), including High Performance Liquid Chromatography (HPLC), Capillary Electrophoresis (CE) and various bromination methods.
Preferably, the substrate used in the method of the invention is subjected to a degas treatment before being contacted with the monomer(s).
The membrane system may be made by a batch method or a continuous method.
In the batch method, the monomer(s) is applied to the substrate, which may be, for example, in the form of a sheet, and the monomer(s) subjected to polymerization. The monomer(s) may be applied by simply dipping the substrate into a monomer solution. Preferably dipping of the substrate into the monomer solution takes place at a controlled speed to ensure a consistent coating of the monomer solution.
Polymerization of the monomer(s) may be achieved by any method that is suitable for the monomer(s) used. Initiation of the polymerization may be conducted by a photo, redox or thermal methods.
In the case of a photopolymerization, the substrate may be coated with the monomer(s) and photoinitiator(s) polymerised by being irradiated for a predetermined time.
With thermal polymerization, the substrate may be coated with the monomer(s) and optionally an initiator (eg APS) then heated to a temperature at which polymerization occurs.
In the case of redox polymerization, a co-initiator (eg TEMED) may be applied to the substrate (eg by spraying), followed by application of the monomer(s) with an initiator, (eg APS). The substrates may then transferred into the reaction chamber for the polymerization.
As already mentioned, the polymeric membrane system of the present invention may be prepared by a continuous method, in which case, the substrate, in a continuous form (eg a continuous web) is continuously contacted with a monomer(s) followed by polymerization of the monomer(s).
Where appropriate, the polymerization methods used for the continuous method may be those discussed above in relation to the batch method.
Preferably, the substrate is degassed before being contacted with the monomer. We have found that with degassing treatment, the polymerization gave a lower induction period and the resultant membrane gave lower endosmosis.
Thickening agents have been used to alter the viscosity of the monomer composition before applying the monomer to the substrate. We however found that when we used un-thickened monomer solution and polymerized it, the resultant material appeared no different from the wet substrate. Indeed, we initially believed that the polymerization had been unsuccessful. We had expected to get a membrane that looked similar to the membranes in the prior art with a glossy appearance. However, on closer inspection there appeared to be a polymeric film on the substrate. The membranes were found to be water-resistant and had a defined pore size.
Depending on the application, it may be necessary to add a thickening agent to the monomer solution.
For the purposes of further illustrating the present invention, we will now describe the invention in reference to polyacrylamide gels as the polymeric gel used in the polymeric membrane system, however, it will be clear to the skilled reader that any monomer system that is capable of forming a membrane may be used with the present invention.
The crosslinked polymer gel may be prepared from monomer(s) having the formula H2Cxe2x95x90CR5xe2x80x94COxe2x80x94NR3R4 where R3, R4 and R5 are each independently H or alkyl optionally monosubstituted by, for example, OH or C(O)CH2C(O) CH3. Examples of monomers include acrylamide, acrylamide derivatives or acrylamide substitutes known to the art such as N,N-dimethylacrylamide, methacrylamide, methyloylacrylamide, propylacrylamide, dipropyl acrylamide, isopropyl acrylamide, diisopropyl acrylamide, lactyl acrylamide, methoxyacrylamide and mixtures thereof. Preferably the monomer is acrylamide.
These polyacrylamide gel may be produced by copolymerization of the momomer(s) with a conventional crosslinking agent such as N,Nxe2x80x2-methylene bisacrylamide, otherwise known as BIS. Other known crosslinking agents include but not limited to the following ethylene glycol diacrylate, dihydroxy ethylene-bisacrylamide (DHEBA), N,Nxe2x80x2propylenebisacrylamide, diacrylamide dimethylether, 1,2-diacrylamide ethyleneglycol, ethyleneureabisacrylamide, N,Nxe2x80x2bisacrylylcystamine and bisacrylamide methylether (BAME). As for BIS, the double bonds of these crosslinking agents are of the same type.
The crosslinked polymer gel may be produced by using the monomer with the following formula: 
wherein
X and Xxe2x80x2 are independently selected from the group consisting of xe2x80x94Oxe2x80x94,xe2x80x94Sxe2x80x94 and xe2x80x94NRxe2x80x94, where R is H, alkyl or cycloalkyl,
R1,R2 is a C1-C4 alkyl group,
Y is an optionally substituted non-aromatic divalent linking group, and
Z is O or S. Such crosslinked polymers are described in International Patent Application PCT/AU97/00437, the whole disclosure of which is incorporated herein by reference.
The crosslinker may be a combination of crosslinkers at least one of which has at least three crosslinkable functional groups, wherein at least one of the crosslinkable functional groups is the group CH2xe2x95x90C(R)xe2x80x94COxe2x80x94, where R is H or optionally substituted alkyl, as described in PCT/AU00/00238 the disclosure of which is incorporated herein by reference. The crosslinker having at least three crosslinkable functional groups is a compound of Formula I or Formula II 
wherein, in Formula I:
C represents a ring structure of the crosslinker molecule which is connected with at least 3 functional groups xe2x80x94Yxe2x80x94CZC(R)xe2x95x90CH2 which functional groups may be the same or different;
Y in each functional group is independently selected from single bond, N, O or S;
Z in each functional group is independently selected from O or S; or Z may be two hydrogens, a hydrogen an optionally substituted alkyl, or two optionally substituted alkyl groups, and
R in each functional group may be the same or different and selected from hydrogen or optionally substituted alkyl; and
In Formula II:
D represents a backbone chain of the crosslinker which is connected with at least three functional groups xe2x80x94Yxe2x80x94CZC(R)xe2x95x90CH2 which functional groups are the same or different;
Y in each functional group is the same or different and selected from the group consisting of a single bond, N, O or S;
Z in each functional group may is the same or different and selected from O or S; and
R in each functional group is the same or different and selected from hydrogen or optionally substituted alkyl.
As used herein the term xe2x80x9con-aromatic hydrocarbyl groupxe2x80x9d means any divalent group comprising carbon and hydrogen which does not include an aromatic or heteroaromatic ring.
As used herein the term xe2x80x9calkylenexe2x80x9d, used either alone or in compound words such as xe2x80x9coxyalkylenexe2x80x9d, xe2x80x9ccarbonylalkylenexe2x80x9d denotes straight chain and branched C1-10 alkylene groups. Examples include methylene, ethylene, propylene, isopropylene, butylene, isobutylene, sec-butylene, pentylene, isopentylene, sec-pentylene, 1,2-dimethylpropylene, 1,1-dimethylpropylene, hexylene, 4-methylpentylene, 1-methylpentylene, 3-methylpentylene, 1,1-dimethylbutylene, 2,2-dimethylbutylene, 3,3-dimethylbutylene, 1,2-dimethylbutylene, 1,3-dimethylbutylene, 1,2,2-trimethylpropylene, 1,1,2-trimethylpropylene, heptylene, 5-methylhexylene, 1-methylhexylene, 2,2-dimethylpentylene, 3,3-dimethylpentylene, 4,4-dimethylpentylene, 1,2-dimethylpentylene, 1,3-dimethylpentylene, 1,4-dimethylpentylene, 1,2,3-trimethylbutyl, 1,1,2-trimethylbutylene and the like.
The term xe2x80x9ccycloalkylenexe2x80x9d, used alone or in compound words such as xe2x80x9calkylenecycloalkylenexe2x80x9d denotes divalent cyclic C3-7, alkyl groups. Examples include cyclopropyl, cyclobutyl, cyclopentyl and cycloheptyl.
The term xe2x80x9cheterocyclylxe2x80x9d as used alone or in compound names such as xe2x80x9calkyleneheterocyclylxe2x80x9d denotes 5 or 6 membered heterocyclic rings. Examples of 5 or 6 membered heterocyclic rings include pyrrolidine, imidazolidine, pyrazolidine, thiazolidine, isothiazolidine, oxazolidine, piperidine and piperazine.
In this specification the term xe2x80x9coptionally substitutedxe2x80x9d means that a group may or may not be further substituted with one or more groups selected from alkyl, cycloalkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkynyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, haloalkenyloxy, nitro, amino, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroheterocyclyl, alkylamino, dialkylamino, alkenylamine, alkynylamino, acyl, alkenacyl, alkynylacyl, acylamino, diacylamino, acyloxy, alkylsulphonyloxy, heterocyclyl, heterocycloxy, heterocyclamino, haloheterocyclyl, alkylsulphenyl, carboalkoxy, alkylthio, acylthio, phosphorous-containing groups such as phosphono and phosphinyl, and groups of the formula 
where X, Xxe2x80x2 and Z are as defined above.
The term xe2x80x9calkylxe2x80x9d, used either alone or in compound words such as xe2x80x9chaloalkylxe2x80x9d or xe2x80x9calkylthioxe2x80x9d, denotes straight chain or branched C1-6 alkyl groups. Examples include methyl, ethyl, propyl, isopropyl and the like.
The term xe2x80x9calkoxyxe2x80x9d denotes straight chain or branched alkoxy, preferably C1-10 alkoxy. Examples include methoxy, ethoxy, n-propoxy, isopropoxy and the different butoxy isomers.
The term xe2x80x9calkenylxe2x80x9d denotes groups formed from straight chain, branched or mono- or poly-cyclic alkenes including ethylenically mono- or poly-unsaturated alkyl or cycloalkyl groups as previously defined, preferably C2-10 alkenyl. Examples of alkenyl include vinyl, allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-octenyl, cyclooctenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 1-decenyl, 3-decenyl, 1,3-butadienyl, 1-4,pentadienyl, 1,3-cyclopentadienyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5-cycloheptatrienyl, 1,3,5,7-cyclooctatetraenyl.
The term xe2x80x9chalogenxe2x80x9d denotes fluorine, chlorine, bromine or iodine, preferably chlorine or fluorine.
The term xe2x80x9cacylxe2x80x9d used either alone or in compound words such as xe2x80x9cacyloxyxe2x80x9d, xe2x80x9cacylthioxe2x80x9d, xe2x80x9cacylaminoxe2x80x9d or diacylaminoxe2x80x9d denotes carbamoyl, aliphatic acyl group and acyl group containing a heterocyclic ring which is referred to as heterocyclic acyl, preferably C1-10 acyl. Examples of acyl include carbamoyl; straight chain or branched alkanoyl, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl; alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl or heptyloxycarbonyl; cycloalkylcarbonyl such as cyclopropylcarbonyl cyclobutylcarbonyl, cyclopentylcarbonyl or cyclohexylcarbonyl; alkylsulfonyl, such as methylsulfonyl or ethylsulfonyl; alkoxysulfonyl, such as methoxysulfonyl or ethoxysulfonyl; heterocyclylcarbonyl; heterocyclylalkanoyl, such as pyrrolidinylacetyl, pyrrolidinylpropanoyl, pyrrolidinylbutanoyl, pyrrolidinylpentanoyl, pyrrolidinylhexanoyl or thiazolidinylacetyl; heterocyclylalkenoyl, such as heterocyclylpropenoyl, heterocyclylbutenoyl, heterocyclylpentenoyl or heterocyclylhexenoyl; or heterocyclylglyoxyloyl, such as, thiazolidinylglyoxyloyl or pyrrolidinylglyoxyloyl.
Free radical polymerization of vinyl monomer(s) can be initiated using a variety of different initiating systems. One of the chemical polymerizations is performed using ammonium persulfate (APS) as the initiator and N,N,Nxe2x80x2Nxe2x80x2-tetramethylenediamine (TEMED) as the activator.
An advantage of using photo-polymerization is that very high conversions of monomer to polymer can be achieved. Photo-polymerization systems are theoretically well suited to this application as radicals are continuously produced as long as light is being absorbed (Caglio, S.; Righetti, P. G. Electrophoresis 1993, 14, 554-558). This is in contrast to the persulphate redox polymerization where, once the initiators have been mixed together, there is a limited time for which they can be used and production of radicals is continuous. Whereas for photo-polymerization systems, reaction does not occur until it is hit with a source of light (Chiari, M.; Micheletti, C.; Righetti, P. G.; Poli, G. J. Chromatography 1992, 598, 287-297).
Photoinitiator systems are usually composed of a dye (which absorbs light energy) and an oxidiser/reducer couple (which produce the free radicals). A selection of photoinitiator systems were used, including the traditionally used methylene blue (MB)/sodium toluene sulfinate (STS)/ and diphenyliodonium chloride (DPIC). Good results were obtained by the use of riboflavin 5xe2x80x2-monophosphate sodium salt dihydrate (RMNxe2x80x94Na)/STS and DPIC system (Structures of photo-initiating systemxe2x80x94see FIG. 2).
The wavelengths via which the dye absorbs incident light were measured on a UV spectrophotometer to determine the most appropriate light source (See FIG. 3). The main features of the absorption profile are the two areas where riboflavin strongly absorbs light energy, one around 380 nm (UV) and one further up at around 450 nm (more in the visible light range). This suggests that the reaction to form the initiating radicals can occur using either UV radiation or visible light, such as produced from a fluorescent lamp. The intensity of the light also has a bearing on the rate of the reaction, the more intense the light, the faster the rate of reaction. Both fluorescent (produces visible light) and UV lamps have been thoroughly tested during the course of our investigation. The particular application might determine the light system used.
Without the present invention being bound by theory, it is generally believed that the polyacrylamide formed from photo-polymerization contains chemically bound sulfinates and DPIC residues. These are both non-acidic and the oxidizing power of the residues and unreacted species is considerably lower than the persulfate chemical polymerization currently used (Lyubimova, T.; Caglio, S.; Gelfi, C.; Righetti, P. G.; Rabilloud, T. Electrophoresis 1993, 14, 40-50; Rabilloud, T.; Vincon, M.; Garin, J. Electrophoresis 1995, 16(8), 1414-1422).
The concentration of the photoinitiator system used for the polymerization is preferably kept low as practically possible. This will minimize the chance of the initiator residues contained within the polymer network interfering in any way with the use of the membrane.
Whilst the polymerization can be conducted under any atmosphere, it is preferable to have an oxygen-free environment. The presence of oxygen in the polymerization zone will have the effect of slowing down the reaction and delaying gel time, as oxygen acts as a retarder/inhibitor in the photoinitiated system (Margerum, J. D.; Lackner, A. M.; Little, M. J.; Petrusis, C. T. J. Phys. Chem. 1971, 75, 3066-3074; Gelfi, C.; De Besi, P.; Alloni, A.; Righetti, P. G.; Lyubimova, T.; Briskman, V. A. J. Chromatography 1992, 598, 277-285.). Therefore the amount of oxygen is preferably controlled in the production process.
Preferably, greater than 95% more preferably greater than 99% conversion is achieved in the method of the present invention. Such high conversions can be obtained by controlling the reaction conditions carefully. It is particularly important to maintain the oxygen concentration as low as possible. An atmosphere of an inert gas (eg nitrogen or argon) should blanket over both the coater and the polymerization zones. This will allow polymerization to occur at peak efficiency, and ensure that the conversion will be pushed as high as possible.
The following embodiments are provided for the purpose of further illustrating the present invention but in no way are to be taken as limiting the present invention.